Rollover Trial Safety and Tolerability of Combination Tipranavir and Ritonavir Use in HIV 1 Infected Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00146328
First received: September 5, 2005
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

The objective of this study is to determine the long term safety and tolerability of multiple oral doses of tipranavir (Aptivus) and ritonavir with a focus on the long term safety of the development dose (500 mg tipranavir/200 mg ritonavir BID) when administered with other antiretroviral medications.


Condition Intervention Phase
HIV Infections
Drug: Tipranavir
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Long Term Open Label Rollover Trial Assessing the Safety and Tolerability of Combination Tipranavir and Ritonavir Use in HIV-1 Infected Subjects

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Haemoglobin [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - White Blood Cell ct. [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Platelets [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Prothrombin Time [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Sodium [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Potassium [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Calcium [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Phosphate [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Carbon Dioxide [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Aspartate Aminotransferase (AST/GOT,SGOT) [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Alanine Aminotransferase (ALT/GPT,SGPT) [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Alkaline Phosphatase [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Amylase [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Creatine Phosphokinase [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Lipase [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Glucose [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Cholesterol, Total [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Creatinine [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Bilirubin, Total [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Triglycerides [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Uric Acid [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 - Albumin [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 or 4 -Low-density Lipoprotein (LDL) [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: No ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.

  • Number of Patients With Adverse Events Leading to Death [ Time Frame: End of Trial (>288 weeks) ] [ Designated as safety issue: Yes ]
    NIH Division of AIDS (DAIDS) Table for Grading Severity of Adult Adverse Experiences, December 2004.


Secondary Outcome Measures:
  • Change From Baseline in Human Immunodeficiency Virus-Ribonucleic Acid (HIV-RNA) Viral Load - Last Observation Carried Forward (LOCF) [ Time Frame: Baseline to 192-240 week time interval ] [ Designated as safety issue: No ]
    Change from baseline in Human Immunodeficiency Virus-Ribonucleic Acid (HIV-RNA) viral load with last observation carried forward (LOCF)

  • Change From Baseline in CD4 Cell Count (LOCF) [ Time Frame: Baseline to 192-240 week time interval ] [ Designated as safety issue: No ]
    Change from baseline in CD4 cell count with last observation carried forward(LOCF).


Enrollment: 997
Study Start Date: April 2001
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Patients With Varying Degrees of Tipranavir Treatment Experience
Drug: Tipranavir
Experimental: Group 2
Highly Tipranavir Treatment Experienced Patients
Drug: Tipranavir
Experimental: Group 3
Tipranavir Treatment Naive Patients
Drug: Tipranavir

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA

  1. Ability and willingness to give written informed consent in accordance with institutional and federal guidelines and to comply with the investigational nature of the study and the related requirements.
  2. All subjects must have successfully completed participation in a combination tipranavir/ritonavir trial or have confirmed virologic failure in the 1182.12 or 1182.48 trials and are not able to obtain TPV by prescription. Successful completion of participation is defined as conclusion of required subject-weeks on assigned dosing (trial specific) and completion of required visits.
  3. Male and female subjects 18 years and over.
  4. Presence of Human Immunodeficiency Virus 1 (HIV-1) infection as documented by any licensed Enzyme Linked immunosorbent Assay (ELISA) test kit and confirmed by Western Blot, or HIV-1 culture, or HIV-1 antigen, or plasma HIV 1 Ribonucleic Acid (RNA) or a second antibody test by a method other than ELISA at any time prior to study entry.
  5. Adherence to previous tipranavir/ritonavir dosing protocol and adherence to visit requirements of previous protocol (as assessed by principal investigator).
  6. Acceptable screening laboratory values that indicate adequate baseline organ function. Laboratory values are considered to be acceptable if the following apply:

    • Total Cholesterol ≤400 mg/dl (<Common Toxicity Criteria (CTC) Grade 2).
    • Total Triglycerides ≤750 mg/dl (<Division of AIDS (DAIDS) Grade 2).
    • Alanine aminotransferase (ALT) ≤3.0x upper limit of normal (ULN) and Aspartate aminotransferase (AST) ≤2.5x ULN (<DAIDS Grade 1).
    • Any Grade Gamma Glutamyl transpeptidase(GGT) is acceptable.
    • Any Grade creatinine kinase is acceptable as long as there is no concurrent myopathy.
    • All other laboratory test values ≤DAIDS Grade 1.

EXCLUSION CRITERIA

  1. Female subjects who are of reproductive potential who:

    • Have a positive serum beta human chorionic gonadotropin (B HCG) at Screening/Enrollment Visit.
    • Are not willing to use a reliable method of barrier contraception (such as diaphragm or condoms).
    • Are breast-feeding.
  2. Subjects who are actively using injection drugs or other substance abuse (such as extensive alcohol or narcotic use) which is considered by the investigator to be a significant impairment to health and to protocol adherence.
  3. Any medical condition(s) which, in the opinion of the investigator, would interfere with the subject's ability to participate in or adhere to the requirements of this protocol.
  4. History of any illness or drug allergy which, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering tipranavir/ritonavir to the subject.
  5. Active use of any of the following:

    • Investigational HIV-1 vaccines.
    • Any new investigational antiretroviral agent that was not approved for use in the patients prior tipranavir trial.
    • Medications excluded during the trial period (see Section 4.2).
    • Herbal medications (e.g., St. John's Wort).
  6. Active HIV-related or non HIV-related illness that may be negatively affected by use of tipranavir/ritonavir as determined by the investigator.

    If a subject must temporarily discontinue tipranavir/ritonavir at the recommendation of the investigator (at the completion of the previous tipranavir trial), then the subject may enroll in 1182.17 once the clinical illness has resolved, and after approval from the Boehringer Ingelheim Clinical Monitor or Local Clinical Monitor.

  7. Clinically significant liver disease in the 90 days prior to baseline visit, regardless of baseline AST and/or ALT values.
  8. Hypersensitivity to tipranavir or ritonavir.
  9. Voluntary discontinuation of antiretroviral therapy (including tipranavir/ritonavir) for more than seven days from completion of previous tipranavir trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00146328

  Show 233 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00146328     History of Changes
Other Study ID Numbers: 1182.17
Study First Received: September 5, 2005
Results First Received: May 26, 2009
Last Updated: January 31, 2014
Health Authority: Argentina: A.N.M.A.T. (Administración Nacional de Medicamentos, Alimentos y Tecnología)
Australia: Responsilble Ethics Committee
Belgium: Federal Agency for Medicines and Health Products, FAMHP
United States: Food and Drug Administration

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir
Tipranavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 23, 2014